Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The reverse transcriptase inhibitor 9-[2-(phosphonomethoxy)propyl]adenine (PMPA; tenofovir) was previously found to offer strong prophylactic and therapeutic benefits in an infant macaque model of pediatric human immunodeficiency virus (HIV) infection. We now summarize the toxicity and safety of PMPA in these studies. When a range of PMPA doses (4 to 30 mg/kg of body weight administered subcutaneously once daily) was administered to 39 infant macaques for a short period of time (range, 1 day to 12 weeks), no adverse effects on their health or growth were observed; this included a subset of 12 animals which were monitored for more than 2 years. In contrast, daily administration of a high dose of PMPA (30 mg/kg subcutaneously) for prolonged periods of time (>8 to 21 months) to 13 animals resulted in a Fanconi-like syndrome (proximal renal tubular disorder) with glucosuria, aminoaciduria, hypophosphatemia, growth restriction, bone pathology (osteomalacia), and reduced clearance of PMPA. The adverse effects were reversible or were alleviated following either complete withdrawal of PMPA treatment or reduction of the daily regimen from 30 mg/kg to 2.5 to 10 mg/kg subcutaneously. Finally, to evaluate the safety of a prolonged low-dose treatment regimen, two newborn macaques were started on a 10-mg/kg/day subcutaneous regimen; these animals are healthy and have normal bone density and growth after 5 years of daily treatment. In conclusion, our findings suggest that chronic daily administration of a high dose of PMPA results in adverse effects on kidney and bone, while short-term administration of relatively high doses and prolonged low-dose administration are safe.
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PMID:Biological effects of short-term or prolonged administration of 9-[2-(phosphonomethoxy)propyl]adenine (tenofovir) to newborn and infant rhesus macaques. 1510 94

Toxic nephropathy is an important cause of reversible renal injury. This article focuses on the nephrotoxicity of several new therapeutic compounds. Selective cyclooxygenase-2 inhibitor is associated with sodium retention, hypertension, ankle edema, and acute renal failure. The incidence of renal complication is similar to conventional nonsteroidal anti-inflammatory drugs. Bisphosphonates, especially when used in high dose for prolonged duration, can cause toxic acute tubular necrosis and renal failure. Pamidronate is also associated with a specific form of collapsing focal segmental glomerulosclerosis similar to one found in patients with human immunodeficiency virus (HIV) infection. Acyclic nucleoside phosphonate, a new group of antiviral agents, can cause Fanconi-like syndrome and progressive renal impairment. On the other hand, indinavir, a potent protease inhibitor for the treatment of HIV infection, can cause crystalluria, renal stone, acute tubular obstruction and chronic interstitial nephritis. Intravenous immune globulin and hydroxyethyl starch, a new plasma expander, are associated with acute renal failure with characteristic renal histology known as osmotic nephrosis. In short, physicians should be cautious about possible renal toxicity during the use of any new therapeutic agents.
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PMID:Nephrotoxicity related to new therapeutic compounds. 1595 51